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Abstract #0168

Hyperpolarised [2-13C]Pyruvate Uniquely Reveals the Role of Acetylcarnitine as a Mitochondrial Substrate Buffer in the Heart

Marie Allen Schroeder1, Helen J. Atherton1, Philip Lee2, Michael S. Dodd1, Lowri E. Cochlin1, Kieran E. Clarke1, George K. Radda1,2, Damian J. Tyler1

1Physiology, Anatomy and Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom; 2Biomedical Sciences Institute, Singapore Bioimaging Consortium, Singapore, Singapore

Mitochondrial acetylcarnitine may be involved in balancing the glucose-fatty acid cycle in the heart. Here, we used hyperpolarised [2-13C]pyruvate with magnetic resonance spectroscopy to monitor the incorporation of acetyl-CoA formed by pyruvate dehydrogenase into the acetylcarnitine pool, and the metabolites of the Krebs cycle, in real-time and in vivo. Our results demonstrated that most pyruvate-derived acetyl-CoA entering the Krebs cycle does not immediately condense with oxaloacetate, but is first converted to acetylcarnitine. Examination of acetylcarnitine production from pyruvate-derived acetyl-CoA in vivo revealed that acetylcarnitine provides a rapidly mobilised mitochondrial buffer for oxidative substrate and may be fundamental in maintaining high, constant ATP levels in the heart.